Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dietary Cholesterol and Adipose Tissue Inflammation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03729141
Recruitment Status : Not yet recruiting
First Posted : November 2, 2018
Last Update Posted : June 5, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:

Hypothesis: increasing dietary cholesterol in humans will increase visceral, but not subcutaneous adipocyte size, free cholesterol content, and inflammatory gene expression.

Visceral and abdominal subcutaneous adipose tissue biopsies will be obtained from non-obese subjects undergoing elective abdominal surgery at Wake Forest Baptist Medical Center after 3 weeks of zero (control) or 1g dietary cholesterol supplementation. Blood samples will also be taken before and after 3 weeks of dietary supplementation (0 vs. 1g dietary cholesterol) to measure plasma lipids levels, and ex vivo monocyte chemotaxis. Blood will also be used to isolate CD14+ monocytes for RNA extraction and storage for future transcriptome studies. Measurements of adipocyte size, free cholesterol content, and inflammatory gene and protein expression in the adipose tissue biopsies to test the hypothesis. Adipocytes and the stromal vascular fraction will be isolated and evaluated for CD14+ macrophages for RNA extraction and storage for future transcriptome analysis.


Condition or disease Intervention/treatment Phase
Cholesterol Dietary Supplement: Added Cholesterol Other: No Added Cholesterol Not Applicable

Detailed Description:
A Wake Forest School of Medicine Clinical Research Unit-based pilot study will be conducted in which subjects scheduled to undergo elective intra-abdominal surgery at Wake Forest Baptist Medical Center (i.e., cholecystectomy, Nissen fundoplication, hernia repair, etc.) will be recruited. Subjects will be randomly and blindly assigned to receive daily treats (cookie, brownie, or muffin) containing either no added cholesterol (control) or 1g of cholesterol/day (~0.4 mg/Kcal cholesterol) for 3 weeks prior to surgery. Three weeks for the length of cholesterol supplementation has been chosen because this is within the duration of human egg-consumption studies in which significant elevations in plasma LDL concentrations occurred. A blood sample will be taken from each participant at baseline before starting the supplementation period and after 3 weeks of 0 or 1g/day cholesterol supplementation, at the time of scheduled surgery. The blood samples will be used for measurement of lipid profile, ex vivo monocyte chemotaxis, and for monocyte RNA isolation. During surgery, abdominal wall subcutaneous adipose tissue and mesenteric (visceral) adipose tissue samples will be obtained. Aliquots of adipose tissue will be fixed overnight for histology and measurement of adipocyte size distribution and CD68 immunostaining, flash frozen and stored for cholesterol quantification by gas liquid chromatography, extracted to isolate RNA and protein for quantitative real time PCR and immunoblotting of inflammatory gene and protein expression, and collagenase digested to isolate adipocytes and stromal vascular cell fraction macrophages which will be used to extract and store RNA for future transcriptome analyses.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Cholesterol Mobilization and Adipocyte Function in Humans
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Added Cholesterol Dietary Supplement: Added Cholesterol
Participants assigned to the added cholesterol group will receive snacks containing added cholesterol (1g/day) for 3 weeks prior to surgery.

Active Comparator: No Added Cholesterol Other: No Added Cholesterol
Participants assigned to the no added cholesterol group will receive snacks containing no added cholesterol for 3 weeks prior to surgery.




Primary Outcome Measures :
  1. Plasma total [ Time Frame: up to 6 weeks after surgery ]
    Plasma will be used to measure plasma total

  2. Adipocyte size [ Time Frame: within 6 weeks after surgery ]
    Adipocyte size will be evaluated by histology by microscopic examination and morphometry.

  3. Lipoprotein cholesterol levels [ Time Frame: up to 6 weeks after surgery ]
    Plasma will be used to measure lipoprotein cholesterol levels.


Other Outcome Measures:
  1. Plasma lipid levels [ Time Frame: up to 12 weeks ]
    Blood samples will be collected from subjects at baseline and at the time of surgery in which snacks containing either no added cholesterol or 1g/day added cholesterol were eaten for three weeks prior to surgery. Plasma lipid levels will be measured. In addition blood will be used to isolate CD14+ monocytes for RNA extraction and storage for future transcriptome studies.

  2. Ex vivo monocyte chemotaxis [ Time Frame: up to 12 weeks ]
    Blood samples will be collected from subjects at baseline and at the time of surgery in which snacks containing either no added cholesterol or 1g/day added cholesterol were eaten for three weeks prior to surgery. Ex vivo monocyte chemotaxis will be measured. In addition blood will be used to isolate CD14+ monocytes for RNA extraction and storage for future transcriptome studies.

  3. Gene expression [ Time Frame: within 20 weeks of surgery. ]
    Visceral and subcutaneous adipose tissue will be collected from subjects in which snacks containing either no added cholesterol or 1g/day added cholesterol were eaten for three weeks prior to surgery. Tissue samples will be taken from non-obese participants undergoing elective abdominal surgery to be used to measure inflammatory gene expression.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age:18 to 70 years old
  • Operated on by one of the study team surgeons at Wake Forest Baptist Medical Center.

Exclusion Criteria:

  • History of liver disease (e.g., autoimmune hepatitis, Wilson's disease, hemochromatosis, 1 anti-trypsin deficiency), as determined by chart review
  • Childs A, B, or C cirrhosis, as determined by chart review
  • Present diagnosis/treatment of malignancy other than non-melanoma skin cancer
  • Baseline INR > 1.8, as determined by chart review or need for continuous anticoagulation with warfarin or heparin
  • Platelets <50,000 as determined by chart review
  • Active immunomodulation therapy for chronic inflammatory diseases, including but not limited to rheumatoid arthritis, psoriasis, SLE, sarcoidosis, or inflammatory bowel disease
  • Diabetes mellitus requiring treatment with oral agents or insulin
  • Taking Questran, Colestid, or Zetia
  • BMI over 30

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03729141


Contacts
Layout table for location contacts
Contact: Janet Sawyer 336-716-3784 jsawyer@wakehealth.edu
Contact: Richard Weinberg, MD 336-713-7330 weinberg@wakehealth.edu

Locations
Layout table for location information
United States, North Carolina
Wake Forest Baptist Medical Center Not yet recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Janet Sawyer    336-716-6784    jsawyer@wakehealth.edu   
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
Layout table for investigator information
Principal Investigator: Richard Weinberg, MD Wake Forest University Health Sciences
Study Chair: John Parks, Ph.D Wake Forest University Health Sciences

Layout table for additonal information
Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03729141     History of Changes
Other Study ID Numbers: IRB00023743
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: June 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wake Forest University Health Sciences:
Cholesterol
Adipocyte
Macrophage